We will finalize our evaluation of the in vitro behaviour patterns of feline gingival fibroblasts derived from cats with normal gingiva and from the same cats after 6 months of daily administration of phenytoin. Analyses in progress reveal that dramatic differences in behaviour patterns exist among such cell strains. Data are being analyzed using Spearman rank correlation. The major effort in fibroblast cloning will continue. Enormous success has been achieved to date; our cloning succes rate has improved to well over 50% of all single cells seeded, while comparable figures from the literature are 2-3%. We note significant inter-cone differences in protein synthesis, collagen production, cell size distribution and replicative lifespan in culture. Planned experiments include evaluation of the effects of phenytoin upon numerous clones after short-term and chronic exposure in vitro. Collagenolytic activity will also be evaluated. The electron microscopic appearance of cloned gingival fibroblasts is proceeding on schedule, and we anticipate reporting our first data at the I.A.D.R. meeting. We have been provided with pure samples of 3 phenytoin metabolites, isolated from dog urine. The studies of the effects of these metabolites upon cloned and mass culture human and feline gingival fibroblasts will proceed as planned. The characterization of glycosaminoglycans produced by human gingival fibroblasts from responder and nonresponder human gingiva is proceeding. Preliminary data are not yet available, but the methodologies required have now been worked out in our lab.